Heart failure affects approximately 5 million Americans. Despite significant advances in medical therapy, there is little to definitively offer patients other than heart transplantation. Ventricular restraint therapy is a new non-transplant surgical treatment for heart failure in which the entire heart is wrapped with a prosthetic material with the intent to provide mechanical support from the outside of the heart and thereby prevent and reverse ventricular dilation and remodeling, a key feature in the progression of heart failure whereby the failing heart dilates and enlarges, eventually leading to deteriorating function. Currently available devices apply ventricular restraint in a nonquantitative, non-adjustable manner, which may limit overall effectiveness. Recently, a new ventricular restraint device was developed in which an inflatable balloon lines the inner surface so ventricular restraint pressure can be applied in an adjustable and measurable manner. Studies on sheep with experimentally induced heart failure have shown that this device can produce more robust improvement in heart function and reversal of left ventricular remodeling in comparison to the original non-adjustable prosthetic wraps. The current adjustable device is applied to both ventricles, but ongoing studies have shown that ventricular restraint effects the right and the left ventricle differently, i.e., while ventricular restraint appears to improve indicators of heart muscle oxygenation in the left ventricle, it does not produce this effect in the right ventricle and meanwhile causes decreased delivery of blood to the heart, leading to low blood pressure and thereby limiting the amount of pressure that can be used in ventricular restraint to benefit the left ventricle. The purpose of this study is to test the hypothesis that applying ventricular restraint in isolated manner to the left ventricle only is superior to biventricular restraint by (1) determining what the optimum level of pressure should be to produce optimum oxygenation of the left ventricular heart muscle without causing prohibitively low blood pressure, and (2) determining if isolated left ventricular restraint at this optimal pressure is able to produce a more robust long-term improvement heart function and the reversal of left ventricular remodeling in the failing sheep heart. We will study this by assessing the effects of this device on myocardial hemodynamics, energetics, and molecular markers of myocardial metabolism. PUBLIC HEALTH RELEVANCE: Heart disease is the leading cause of death in the United States and affects millions of Americans each year. Currently, the only definitive treatment for heart failure, the end result of heart disease, is heart transplantation, but the number of available hearts is limited to around 2500 per year. The use of ventricular restraint devices may significantly impact the public health burden of heart failure by offering a non-transplant surgical therapeutic option for preventing the progression and even reversing the hemodynamic changes associated with heart failure.